Covalent organic framework nanomedicines: Biocompatibility for advanced nanocarriers and cancer theranostics applications

Bioactive Materials, Journal Year: 2022, Volume and Issue: 21, P. 358 - 380

Published: Sept. 14, 2022

Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area. The unique properties of nanomedicines have massive potential in solving longstanding challenges existing drugs, such as poor localization at the tumor site, high doses toxicity, recurrence, immune response. However, inadequate biocompatibility restricts their clinical translation. Therefore, advanced nanomaterials with enhanced therapeutic efficiency are highly desired to fast-track translation nanomedicines. Intrinsic nanoscale covalent organic frameworks (nCOFs), suitable size, modular pore geometry porosity, straightforward post-synthetic modification via simple transformations, make them incredibly attractive future ability COFs disintegrate slightly acidic microenvironment also gives competitive advantage targeted delivery. This review summarizes recently published applications delivery, photo-immuno therapy, sonodynamic photothermal chemotherapy, pyroptosis, combination therapy. Herein we mainly focused on modifications enhance biocompatibility, efficacy will provide fundamental knowledge designing biocompatible nCOFs-based help rapid development carriers theranostics.

Language: Английский

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Challenges and new technologies in adoptive cell therapy

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 18, 2023

Abstract Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to subsequent specific enhanced T receptor (TCR)-T and chimeric antigen (CAR)-T therapies, many novel strategies cancer treatment been developed. Owing its promising outcomes, CAR-T therapy has revolutionized field ACTs, particularly hematologic malignancies. Despite these advances, still limitations in both autologous allogeneic settings, including practicality toxicity issues. To overcome challenges, researchers focused on application CAR engineering technology other types immune engineering. Consequently, several new based developed, CAR-NK, CAR-macrophage, CAR-γδT, CAR-NKT. In this review, we describe development, advantages, possible challenges aforementioned ACTs discuss current aimed at maximizing therapeutic potential ACTs. We also provide an overview various gene transduction employed immunotherapy given their importance Furthermore, possibility that capable creating a positive feedback circuit, as healthy systems do, could address flaw single type ACT, thus serve key players future immunotherapy.

Language: Английский

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Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 201 - 201

Published: Jan. 16, 2024

Globally, malignancies cause one out of six mortalities, which is a serious health problem. Cancer therapy has always been challenging, apart from major advances in immunotherapies, stem cell transplantation, targeted therapies, hormonal precision medicine, and palliative care, traditional therapies such as surgery, radiation therapy, chemotherapy. Natural products are integral to the development innovative anticancer drugs cancer research, offering scientific community possibility exploring novel natural compounds against cancers. The role like Vincristine Vinblastine thoroughly implicated management leukemia Hodgkin’s disease. computational method initial key approach drug discovery, among various approaches. This review investigates synergy between techniques, highlights their significance discovery process. transition experimental validation highlighted through vitro vivo studies, with examples betulinic acid withaferin A. path toward therapeutic applications have demonstrated clinical studies silvestrol artemisinin, preclinical investigations trials. article also addresses challenges limitations potential anti-cancer drugs. Moreover, integration deep learning artificial intelligence methods may be useful for enhancing products.

Language: Английский

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Innovative breakthroughs facilitated by single-cell multi-omics: manipulating natural killer cell functionality correlates with a novel subcategory of melanoma cells

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 26, 2023

Melanoma is typically regarded as the most dangerous form of skin cancer. Although surgical removal in situ lesions can be used to effectively treat metastatic disease, this condition still difficult cure. cells are removed great part due action natural killer (NK) and T on immune system. Still, not much known about how activity NK cell-related pathways changes melanoma tissue. Thus, we performed a single-cell multi-omics analysis human study explore modulation cell activity. Cells which mitochondrial genes comprised > 20% total number expressed were removed. Gene ontology (GO), gene set enrichment (GSEA), variation (GSVA), AUCcell differentially (DEGs) subtypes performed. The CellChat package was predict cell-cell contact between subtypes. Monocle program analyzed pseudotime trajectories cells. In addition, CytoTRACE determine recommended time order InferCNV utilized calculate CNV level Python pySCENIC assess transcription factors regulons Furthermore, function experiment confirm TBX21 both A375 WM-115 lines. Following batch effect correction, 26,161 separated into 28 clusters designated cells, neural fibroblasts, endothelial CD4+ CD8+ B plasma monocytes macrophages, dendritic A 10137 further grouped seven subtypes, i.e., C0 BIRC7, C1 CDH19, C2 EDNRB, C3 BIRC5, C4 CORO1A, C5 MAGEA4, C6 GJB2. results AUCell, GSEA, GSVA suggested that CORO1A may more sensitive through positive regulation cell-mediated immunity, while other resistant This suggests intratumor heterogeneity (ITH) melanoma-induced difference cytotoxicity have caused defects. Transcription factor indicated important TF also associated with M1 modules. vitro experiments showed knockdown dramatically decreases cells' proliferation, invasion, migration. differences immunity offer new perspective ITH protective melanoma, STAT1, IRF1, FLI1, modulate responses or

Language: Английский

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Recent Advances in Chitosan and its Derivatives in Cancer Treatment

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: April 28, 2022

Cancer has become a main public health issue globally. The conventional treatment measures for cancer include surgery, radiotherapy and chemotherapy. Among the various available measures, chemotherapy is still one of most important treatments patients. However, cancers faces many problems associated with lot adverse effects, which limit its therapeutic potency, low survival quality discount prognosis. In order to decrease these side effects improve effectiveness patient's compliance, more targeted are needed. Sustainable controlled deliveries drugs controllable toxicities expected address hurdles. Chitosan second abundant natural polysaccharide, excellent biocompatibility notable antitumor activity. Its biodegradability, biocompatibility, biodistribution, nontoxicity immunogenicity free have made chitosan widely used polymer in pharmacology, especially oncotherapy. Here, we make brief review achievements derivatives pharmacology special focus on their agents delivery applications, immunomodulation, signal pathway modulation activity highlight role treatment. Despite large number successful studies, commercialization copolymers big challenge. further development polymerization technology may satisfy unmet medical needs.

Language: Английский

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Redox dyshomeostasis strategy for tumor therapy based on nanomaterials chemistry

Chemical Science, Journal Year: 2022, Volume and Issue: 13(8), P. 2202 - 2217

Published: Jan. 1, 2022

This review summarizes the current progress of redox dyshomeostasis (RDH) strategy for tumor therapy. makes cells more sensitive to therapy patterns through using nanomaterials disrupt homeostasis.

Language: Английский

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Emerging organoid-immune co-culture models for cancer research: from oncoimmunology to personalized immunotherapies

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(5), P. e006290 - e006290

Published: May 1, 2023

In the past decade, treatments targeting immune system have revolutionized cancer treatment field. Therapies such as checkpoint inhibitors been approved first-line in a variety of solid tumors melanoma and non-small cell lung while other therapies, for instance, chimeric antigen receptor (CAR) lymphocyte transfer are still development. Although promising results obtained small subset patients, overall clinical efficacy most immunotherapeutics is limited due to intertumoral heterogeneity therapy resistance. Therefore, prediction patient-specific responses would be great value efficient use costly immunotherapeutic drugs well better outcomes. Because many operate by enhancing interaction and/or recognition malignant target cells T cells, vitro cultures using combination these derived from same patient hold promise predict drug personalized fashion. The two-dimensional lines unreliable altered phenotypical behavior when compared with vivo situation. Three-dimensional tumor-derived organoids, mimic tissue deemed more realistic approach study complex tumor-immune interactions. this review, we present an overview development tumor organoid-immune co-culture models tumor-specific interactions their possible therapeutic infringement. We also discuss applications which advance understanding microenvironment as: (1) Screening inhibition CAR screening manner. (2) Generation reactive lymphocytes adoptive therapies. (3) Studying detect cell-specific roles progression remission. Overall, onco-immune co-cultures might future toward developing approaches increase our

Language: Английский

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Mitochondria-associated ER stress evokes immunogenic cell death through the ROS-PERK-eIF2α pathway under PTT/CDT combined therapy

Acta Biomaterialia, Journal Year: 2023, Volume and Issue: 160, P. 211 - 224

Published: Feb. 14, 2023

Chemodynamic therapy (CDT) can effectively induce immunogenic cell death (ICD) in tumours and is thus a promising strategy for boosting the efficacy of immunotherapy. However, mechanism by which CDT enhances ICD lowers efficiency unknown this restricts its clinical application. In study, second near-infrared (NIR-II) window irradiation-triggered hydrogen peroxide (H2O2) self-supplying nanocomposite ((Cu2Se-CaO2)@LA) was constructed. The modified lauric acid melted heat energy NIR-II irradiation, to expose CaO2 nanoparticles, they then reacted with water produce H2O2 Ca2+. converted hydroxyl radicals photothermal-enhanced process Cu2Se nanocubes. Notably, Ca2+ overload found sequential damage mitochondria endoplasmic reticulum (ER), upregulated PERK-mediated eIF2α phosphorylation pathway caused subsequent ICD. irradiation (Cu2Se-CaO2)@LA also increased reactive oxygen species (ROS) formation sufficient increase dendritic maturation, attracting cytotoxic T lymphocytes, suppressing tumour growth vivo. Overall, we demonstrated that an enhanced under exposure self-supply extensive inducing mitochondria-associated ER stress, represents highly effective amplification STATEMENT OF SIGNIFICANCE: (named (Cu2Se-CaO2)@LA) constructed tested both vitro These nanoparticles antitumor activity as designed. Mechanistically, could upregulate eIF2αphosphorylation pathway, further causing through maturation lymphocyte recruitment augmented activity. This system enhancing tumor immunotherapy provides new insights future studies design refinements.

Language: Английский

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Exploiting the therapeutic implications of KRAS inhibition on tumor immunity

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(3), P. 338 - 357

Published: March 1, 2024

SummaryOver the past decade, RAS oncogenic proteins have transitioned from being deemed undruggable to having two clinically approved drugs, with several more in advanced stages of development. Despite initial benefit KRAS-G12C inhibitors for patients tumors harboring this mutation, rapid emergence drug resistance underscores urgent need synergize these other therapeutic approaches improve outcomes. mutant tumor cells can create an immunosuppressive microenvironment (TME), suggesting increased susceptibility immunotherapies following inhibition. This provides a rationale combining inhibitory drugs immune checkpoint blockade (ICB). However, achieving synergy clinical setting has proven challenging. Here, we explore how understanding impact on TME guide innovative inhibition immunotherapies, review progress both pre-clinical and stages, discuss challenges future directions.

Language: Английский

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Extracellular vesicles as human therapeutics: A scoping review of the literature

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(5)

Published: May 1, 2024

Abstract Extracellular vesicles (EVs) are released by all cells and contribute to cell‐to‐cell communication. The capacity of EVs target specific efficiently deliver a composite profile functional molecules have led researchers around the world hypothesize their potential as therapeutics. While studies EV treatment in animal models numerous, actual clinical benefit humans has more slowly started be tested. In this scoping review, we searched PubMed other databases up 31 December 2023 and, starting from 13,567 records, selected 40 pertinent published testing therapeutics humans. analysis those shows that they small pilot trials with large heterogeneity terms administration route disease. Moreover, absence placebo control most studies, predominant local application formulations inconsistent dose metric still impede comparison across firm conclusions about safety efficacy. On hand, recording some promising outcomes strongly calls out for well‐designed larger test an alternative approach treat human diseases no or few therapeutic options.

Language: Английский

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